DESCRIPTION: (Applicant's Abstract) The objective of this line of research is to gain an understanding of relapse to tobacco dependence and to develop treatments based on this understanding. The first study of the current funding period (N=201 ) was based on the earlier findings of Hall, Munoz & Reus, (1994) who reported that a 10-session mood management intervention was differentially more efficacious than a 5-session standard treatment control for smokers with a history of Major Depressive Disorder (MDD). In a 2 (mood management vs. contact-equivalent, 10 session control) X 2 (2 vs. O mg. nicotine gum) X 2 (MDD history vs. not) design, we found a non-significant difference in efficacy for the mood management intervention for MDD history positive subjects, and no effect for 2 mg. nicotine gum. MDD history positive subjects reported higher levels of negative moods during quitting, and subjects whose negative moods increased during quitting were more likely to continue smoking. The second study (N=200) was a 2 (nortriptyline vs. placebo) X 2 (mood management vs. 5 session standard treatment control) X 2 (MDD history vs. not) design. Results on the first 119 subjects indicate differences between active and placebo nortriptyline at 12 and 24 weeks at p<.05 and differences at 38 weeks at p<. 10. Also, the differential efficacy of mood management for MDD history positive smokers, observed in Hall et al. (1994) re-emerged, suggesting that MDD history positive smokers are differentially helped by therapeutic support, but the precise theory-derived content is not crucial. We now propose two clinical trials. In the first, smokers (N=240) are randomly assigned, in a 3 X 2 design, to nortriptyline, bupropion, or placebo and to medical management alone or medical management-plus psychosocial-support, treated for 12 weeks, and assessed at baseline, 12, 24, 36 and 52 weeks. Variables assessed are smoking behavior and biochemically verified smoking status, diagnosis, demographics and treatment history, state and trait measures of mood, support for quitting smoking, cigarette craving, and medication side effects. In the second study, (N=200) smokers are randomly assigned to either brief (12 week) or extended (52 week ) treatment and to nortriptyline vs. placebo. The brief treatment is the medical management plus psychosocial support condition of the first experiment proposed; extended treatment includes year-long access to drug, group meetings, frequent telephone contacts, and counseling sessions if a relapse is reported. Measures and times of assessment parallel those for the first experiment. In other studies, the cost effectiveness of the treatment conditions is determined. If funded, these studies will provide data about the efficacy and cost-effectiveness of treatments for smoking cessation based on rigorously designed clinical experiments. These data have implications for treatment providers and policy-makers.